Vitamin D is a fat-soluble vitamin that is essential to a number of biological processes, including promoting calcium absorption in the gut, maintaining adequate serum calcium and phosphate concentrations (to enable normal bone mineralization and to prevent hypocalcemic tetany), and is needed for bone growth and bone remodeling by osteoblasts and osteoclasts (van den Berg, H. (1997) Eur. J. Clin. Nutr. 51:S76-9; Institute of Medicine, Food and Nutrition Board. (1997) Dietary Reference Intakes: Calcium, Phosphorus, Magnesium, Vitamin D, and Fluoride. Washington, DC: National Academy Press; Cranney C. et al. (2007) Evidence Report/Technology Assessment No. 158 prepared by the University of Ottawa Evidence-based Practice Center under Contract No. 290-02.0021. AHRQ Publication No. 07-E013. Rockville, Md.: Agency for Healthcare Research and Quality). Insufficient vitamin D may result in thin, brittle, and/or misshapen bones, and is a cause of rickets in children and osteomalacia in adults (DeLuca H. F. (2004) Am. J. Clin. Nutr. 80:1689S-96S; Goldring et al. (1995) Endocrinology. 3rd ed. Philadelphia: W B Saunders, 1204-27; Favus M. J. and Christakos S. (1996) Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism. 3rd ed. Philadelphia, Pa.: Lippincott-Raven). Together with calcium, vitamin D also helps protect older adults from osteoporosis.
Vitamin D also has other roles in human health, including modulation of neuromuscular and immune function and reduction of inflammation. Many genes encoding proteins that regulate cell proliferation, differentiation, and apoptosis are modulated in part by vitamin D (van den Berg (1999); Cranney et al. (2007); Holick, M. F. (2003) Cancer Res. 164:3-28; Hayes et al. (2003) Cell. Mol. Biol. 49:277-300). Vitamin D deficiency has been linked to breast, prostate and colon cancer, as well as autoimmune diseases such as multiple sclerosis, fibromyalgia, rheumatoid arthritis, Grave's disease, lupus, and others. High serum vitamin D3 levels have also been linked to a reduced risk for skin cancers (See Roehr. B. Dermatology Times. July 2009, p. 24)
Vitamin D is naturally produced when the skin is exposed to adequate sunlight, specifically when ultraviolet B (UVB) radiation is strong enough to penetrate the epidermal layers of the skin. Factors that impact the strength UVB radiation, including time of year, latitude, altitude, cloud cover, and pollution, may therefore likewise affect the natural production of vitamin D. For example, complete cloud cover has been shown to reduces UV energy levels by 50% and shade (including that produced by severe pollution) has been shown to reduce UV energy levels by 60% (Wharton B. and Bishop N. (2003) Lancet. 362:1389-400). As vitamin D is naturally present in very few foods, sufficient UVB exposure and/or supplementation is important to maintaining proper Vitamin D levels.
Although sun exposure is critical to natural vitamin D synthesis, UV radiation is a carcinogen responsible for most of the estimated 1.5 million skin cancers and the 8,000 deaths due to metastatic melanoma that occur annually in the United States (Wharton and Bishop, 2003), and lifetime cumulative UV damage to skin is also largely responsible for age-associated dryness and other cosmetic changes. Protecting the skin from the harmful effects of ultraviolet A (UVA) and UVB radiation is therefore critical for reducing the risk of skin cancers and metastatic melanoma, and therefore The American Academy of Dermatology advises that photoprotective measures be taken, including the use of sunscreen, whenever an individual is exposed to the sun (American Academy of Dermatology. Position statement on vitamin D. Nov. 1, 2008). However, sunscreens with a sun protection factor of 8 or more have been shown to block vitamin D producing UV rays, and may therefore interfere with the natural production of vitamin D (Wolpowitz D. and Gilchrest B. A. (2006) J. Am. Acad. Dermatol. 54:301-17).
Various formulations and methods have been developed to treat vitamin D deficient individuals and/or enhance the ability of individuals to produce vitamin D, including vitamin D precursor-based formulations that are applied to the skin and irradiated to cause vitamin D synthesis, as well as topically administered formulations for increasing systemic vitamin D levels. Sunscreen formulations that incorporate vitamins (including vitamin D) for their well-known antioxidant properties are also known in the art. However, sun-protecting formulations incorporating vitamin D in therapeutically effective amounts to achieve and/or maintain adequate systemic vitamin D levels necessary for proper biological functioning, and in particular sun-protecting formulations that provide vitamin D in specific therapeutic amounts that correlate to decreased natural vitamin D production due to the sun-blocking effects of such formulations, are not known. It is therefore objects of the present invention to provide such formulations, and methods of preventing and treating disorders and diseases using such formulations.